Health status improvement with ferric carboxymaltose in heart failure with reduced ejection fraction and iron deficiency

Abstract

Aim: Intravenous ferric carboxymaltose (FCM) has been shown to improve overall quality of life in iron-deficient heart failure with reduced ejection fraction (HFrEF) patients at a trial population level. This FAIR-HF and CONFIRM-HF pooled analysis explored the likelihood of individual improvement or deterioration in Kansas City Cardiomyopathy Questionnaire (KCCQ) domains with FCM versus placebo and evaluated the stability of this response over time.

Methods and results: Changes versus baseline in KCCQ overall summary score (OSS), clinical summary score (CSS) and total symptom score (TSS) were assessed at weeks 12 and 24 in FCM and placebo groups. Mean between-group differences were estimated and individual responder analyses and analyses of response stability were performed. Overall, 760 (FCM, n = 454) patients were studied. At week 12, the mean improvement in KCCQ OSS was 10.6 points with FCM versus 4.8 points with placebo (least-square mean difference [95% confidence interval, CI] 4.36 [2.14; 6.59] points). A higher proportion of patients on FCM versus placebo experienced a KCCQ OSS improvement of ≥5 (58.3% vs. 43.5%; odds ratio [95% CI] 1.81 [1.30; 2.51]), ≥10 (42.4% vs. 29.3%; 1.73 [1.23; 2.43]) or ≥15 (32.1% vs. 22.6%; 1.46 [1.02; 2.11]) points. Differences were similar at week 24 and for CSS and TSS domains. Of FCM patients with a ≥5-, ≥10- or ≥15-point improvement in KCCQ OSS at week 12, >75% sustained this improvement at week 24.

Conclusion: Treatment of iron-deficient HFrEF patients with intravenous FCM conveyed clinically relevant improvements in health status at an individual-patient level; benefits were sustained over time in most patients.

Keywords: Ferric carboxymaltose; Health status; Heart failure with reduced ejection fraction; Iron deficiency; Kansas City Cardiomyopathy Questionnaire; Minimal clinically important difference; Quality of life.

Figure 1

Mean change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score (OSS), clinical summary sore (CSS) and total symptom score (TSS) with ferric carboxymaltose (FCM) versus placebo at weeks 12 and 24 (fixed‐effects model). Fixed‐effects mixed‐model for repeated measures analysis adjusted for study, baseline KCCQ score, age, estimated glomerular filtration rate, diabetes status, sex and left ventricular ejection fraction. CI, confidence interval; LS, least‐square; SD, standard deviation.

Figure 2

Responder analyses across conventional and minimal clinically important difference thresholds for (A) overall summary score (OSS), (B) clinical summary score (CSS), and (C) total symptom score (TSS) Kansas City Cardiomyopathy Questionnaire (KCCQ) domains (fixed‐effects model). Odds ratios (ORs) were obtained from logistic regression models including treatment group, study, and the following baseline factors: KCCQ score, age, estimated glomerular filtration rate, diabetes status, sex and left ventricular ejection fraction. N = number of patients with KCCQ data available at each time point, plus patients who died before assessment and were recorded as ‘not improved’ in the analysis of improvement and ‘deteriorated’ in the deterioration analysis. CI, confidence interval; FCM, ferric carboxymaltose; PBO, placebo.

Figure 3

Response stability analysis – change in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score (OSS) response between week 12 and week 24. N = number of patients that had non‐missing KCCQ data available at both week 12 and week 24. FCM, ferric carboxymaltose.